Bioprocess System

ABSTRACT

A base station (1) and a bioprocess system (3), wherein said base station (1) comprises: a frame or housing (5), wherein said frame or housing comprises a number of valves (7a-f, 9a-d, 11a-f, 13a-e, 15a-f) into which a disposable tubing set (21) during run of the system is provided such that at least one inlet (23a-j) of the disposable tubing set is connected to at least one outlet (25a-f) of the disposable tubing set via a bioprocess separation device (31) of the bioprocess system (3); and a movable pump holding device (35), which can be provided in at least two different positions, whereof one is within the frame or housing (5) and another is at least partly outside the frame or housing (5) and which comprises at least one pump main body (37), said pump main body comprising a connection (39) configured for connecting to a disposable pump connection part (27) comprised in the disposable tubing set (21).

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.16/757,804, filed Apr. 21, 2020, which claims the priority benefit ofPCT/EP2018/079354 filed on Oct. 25, 2018, which claims priority benefitof Great Britain Patent Application No. 1717652.0 filed on Oct. 26,2017, the entire contents of which are incorporated herein by reference.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to a bioprocess system and to a basestation of a bioprocess system.

BACKGROUND OF THE INVENTION

For large bioprocess systems such as chromatography or filtering systemsflow paths within the system have traditionally been provided stationaryin the system as metal or plastic pipes. These pipes need to besanitized between different processes performed in the system.Especially in smaller bioprocess systems the flow paths are nowadaysoften instead provided as flexible, disposable tubing. Hereby the wholeflow path can be exchanged between different processes. When exchangingthe disposable tubing access is needed to valves into which the tubingneed to be connected and pumps to which the tubing should be connected.A problem may be to get good access for an easy exchange of disposabletubing and another problem may be that the systems are bulky.

SUMMARY

An object of the invention is to provide an improved bioprocess systemcomprising a disposable tubing set where the disposable tubing set canbe easily exchanged.

This is achieved in a base station and in a bioprocess system accordingto the independent claims.

According to one aspect of the invention there is provided a bioprocesssystem comprising:

a base station (1) including a frame or housing (5), wherein said frameor housing comprises plural valves (7 a-f, 9 a-d, 11 a-f, 13 a-e, 15a-f) for controlling fluid flow in the system and configured to bereleasably fluidically connectable to a disposable tubing set (21); anda discrete movable pump holding device (35), at least partiallycontainable within the frame or housing (5) and removable therefrom andwhich comprises at least one pump main body (37), said pump main bodycomprising a fluid connection (39) configured to be releasablyconnectable to a pump connection part (27) of the disposable tubing set(21).

Expressed in a different manner the invention provides a base station ofa bioprocess system. Said base station comprises:

-   -   a frame or housing, wherein said frame or housing comprises a        number of valves into which a disposable tubing set during run        of the system may be provided such that at least one inlet of        the disposable tubing set is connected to at least one outlet of        the disposable tubing set via a bioprocess separation device of        the bioprocess system; and    -   a movable pump holding device, which can be provided in at least        two different positions, whereof one is within the frame or        housing and another is at least partly outside the frame or        housing and which comprises at least one pump main body, said        pump main body comprising a connection configured for connecting        to a disposable pump connection part comprised in the disposable        tubing set.

According to another aspect of the invention a bioprocess system isprovided comprising a base station as defined above, a disposable tubingset and a bioprocess separation device.

Herby the pumps of the bioprocess system can be provided both inside theframe or housing and at least partly outside the frame or housing.Hereby the pumps can be easily accessed to change pump heads, forconnection of tubing and for maintenance. The pumps can also be providedcompletely within the frame or housing during run of the system. Herebya less bulky system is provided compared to if the pump heads alwaysneed to be provided outside the system and access for maintenance of thepumps is required.

In one embodiment of the invention said movable pump holding devicecomprises a trolley on wheels and said frame or housing comprises anempty space in a bottom part of the frame or housing for receiving saidmovable pump holding device.

In one embodiment of the invention said frame or housing comprises fourwalls constituting together with a roof of the frame or housingessentially a box, wherein the valves of the frame or housing areprovided on at least three of said four walls and wherein a first wallof said four walls comprises an opening for receiving the movable pumpholding device into an empty space of a bottom part of the frame orhousing and wherein a second wall of said four walls comprises an inletvalve access opening through which access to at least one inlet valvepositioned within the frame or housing is achieved.

In one embodiment of the invention said outlet valves of the frame orhousing are provided on a third wall of said four walls.

In one embodiment of the invention at least five separation devicevalves are provided for receiving the disposable tubing set forcontrolling feeding of a fluid in the disposable tubing set eitherupflow or downflow through or bypass a bioprocess separation deviceconnected to the disposable tubing set.

In one embodiment of the invention said at least five separation devicevalves are provided in the third wall of said four walls but at a lowerposition than the outlet valves.

In one embodiment of the invention said frame or housing comprises aholder for a disposable air trap of the disposable tubing set, whereinsaid holder for a disposable air trap is provided above said inletvalves.

In one embodiment of the invention said valves are pinch valves.

In one embodiment of the invention said disposable tubing set comprises:

-   -   at least one inlet tubing;    -   at least one outlet tubing;    -   at least one disposable pump connection part connected to the        inlet tubing and configured for being connected to a pump main        body;    -   at least one disposable air trap; and    -   two separation device connection points for connection to a        bioprocess separation device,    -   wherein said at least one outlet tubing is connected to said at        least one inlet tubing via the other components of the        disposable tubing set.

In one embodiment of the invention said disposable air trap is adisposable swirl type air trap.

In one embodiment of the invention said disposable tubing set furthercomprises one or more of a disposable UV sensor, a disposable flowsensor, a disposable air sensor, a disposable pH meter, a disposableconductivity meter and a disposable pressure meter.

In one embodiment of the invention all the components of the disposabletubing set are connected and the disposable tubing set can be removedfrom the base station in one piece.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 a and 1 b show two different perspective views of a base stationof a bioprocess system according to one embodiment of the invention.Disposable tubing is connected to the base station.

FIGS. 2 a and 2 b show two different perspective views of a bioprocesssystem according to one embodiment of the invention.

FIGS. 3 a and 3 b show two different perspective views of a base stationaccording to one embodiment of the invention. A movable pump holdingdevice of the base station is here provided outside a frame or housingof the base station.

DETAILED DESCRIPTION OF THE EMBODIMENTS

FIGS. 1 a and 1 b show two different perspective views of a base station1 of a bioprocess system according to one embodiment of the invention.FIGS. 2 a and 2 b show the same base station as shown in FIGS. 1 a and 1b but also connected to a bioprocess separation device 31. Hereby FIGS.2 a and 2 b show two different perspective views of a bioprocess system3 according to one embodiment of the invention. FIGS. 3 a and 3 b showtwo different perspective views of the same base station as shown inFIGS. 1 a and 1 b but without a disposable tubing set connected.

The invention relates to a base station 1 of a bioprocess system 3 andto a bioprocess system 3 comprising such a base station 1. A bioprocesssystem according to the invention comprises a base station 1, adisposable tubing set 21 connected to the base station and a separationdevice 31, such as for example a chromatography column or a filter whichis connected to the disposable tubing set. A separation device 31 is notshown in FIGS. 1 a and 1 b but in FIGS. 2 a and 2 b . The base station 1comprises valves and pumps (further described and numbered below) towhich the disposable tubing set will be connected. Furthermore the basestation 1 suitably comprises some type of controlling capability forcontrolling the valves and pumps during run of the bioprocess system.This control will not be described further.

The base station 1 according to the invention comprises a frame orhousing 5, wherein said frame or housing comprises a number of valves 7a-f, 9 a-d, 11 a-f, 13 a-e, 15 a-f into which a disposable tubing set 21during run of the system is provided such that at least one valve inlet23 a-j is connected to at least one outlet 25 a-f of the disposabletubing set via a bioprocess separation device 31 of the bioprocesssystem 3. In this embodiment of the invention 10 separate inlets 23 a-jare provided. Of course the number of inlets can be varied. In thisembodiment of the invention the inlets 23 a-j are separated into twogroups. A first group comprises four inlets 23 a-d, called first inlets23 a-d, which are provided above a second group comprising six inlets 23e-j, called second inlets 23 e-j. All the inlets 23 a-j can be used forfeeding of for example buffer and sample into the system. Of course thenumber of first and second inlets 23 a-j can be varied. Each of theinlets 23 a-j are during run of the bioprocess system connected to avalve 7 a-f, 9 a-d provided on the base station 1. The valves 7 a-f towhich the second inlets 23 e-j are connected are called second inletvalves 7 a-f and the valves 9 a-d to which the first inlets 23 a-d areconnected are called first inlet valves 9 a-d. Of course the number offirst and second inlet valves 9 a-d, 7 a-f can vary in the base station.In this embodiment of the invention furthermore six different outlets 25a-f of the disposable tubing set 21 are provided. Of course the numberof outlets 25 a-f can vary within the scope of the invention.Accordingly in this embodiment of the invention six outlet valves 11 a-fare provided in the base station 1. During run of the system the outlets25 a-f of the disposable tubing set 21 are provided connected one toeach of these outlet valves 11 a-f. Of course also the number of outletvalves 11 a-f can be varied.

The disposable tubing set 21 will be connected to a bioprocessseparation device 31 during run of the system. The disposable tubing set21 comprises two separation device connection points 71, 73 which can beseen in FIG. 1 a. The disposable tubing is branched such that one branch75 a of the tubing comprises one of the separation device connectionpoints 71 and another branch 75 b comprises the other separation deviceconnection point 73. Furthermore, in this embodiment also a bypassbranch 75 c of the tubing is provided in between the other two branches75 a,b. The three branches are collected into one tubing before andafter the separation device connection points 71, 73. The base station 1comprises separation device valves 13 a-e to which said branches 75a,b,c of the disposable tubing are connected during run. One separationdevice valve is provided on each side of each separation deviceconnection point 71, 73 and one separation device valve is also providedto the bypass branch. By this arrangement of separation device valves 13a-e and the branching of the disposable tubing set 21 for the connectionof the separation device 31, the separation device 31 can be connectedfor both upflow separation (liquid flow upwardly through the device 31)and downflow separation (liquid flow downwardly through the device)without the need of any rearranging of the tubing but only by control ofthe separation device valves 13 a-e. Furthermore the separation device31 can also be bypassed. However, also a simpler arrangement ofseparation device valves without this possibility of switching betweenupflow and downflow separation is covered by the invention. In such asystem no branching of the disposable tubing around the separationdevice connection points 71, 73 is needed and furthermore only threeseparation device valves would be needed.

Furthermore in the base station 1 as shown in FIG. 1 a and 1 b six morevalves 15 a-f are provided. These are provided for allowing bypass orconnection of separate components of the disposable tubing set 21 andare also called component bypass valves 15 a-f. In this embodiment ofthe invention an air trap 63 and a filter cartridge 64 of the disposabletubing set 21 are connected to these component bypass valves 15 a-f. Ifno bypass of these components is needed these valves can be omitted inthe base station 1. An additional air vent valve 65 is in thisembodiment also provided on the frame or housing 5 to which an air venttube from the air trap 63 can be connected.

The valves 7 a-f, 9 a-d, 11 a-f, 13 a-e, 15 a-f, 65 connected to theframe or housing 5 of the base station 1 can for example be pinch valvesor membrane valves.

According to the invention the base station 1 comprises further amovable pump holding device 35. The movable pump holding device 35 canbe provided in at least two different positions, whereof one is withinthe frame or housing 5 and another is at least partly outside the frameor housing 5. The movable pump holding device 35 comprises at least onepump main body 37. In the embodiment shown in FIGS. 1 and 3 the movablepump holding device 35 comprises two pump main bodies 37 however thenumber of pump main bodies can be varied within the scope of theinvention. Each pump main body 37 comprises a pump connection 38configured for connecting to a disposable pump connection part 27, forexample a disposable pump head, comprised in the disposable tubing set21.

In the embodiment of the invention as shown in FIGS. 1-3 the movablepump holding device 35 comprises a trolley on wheels 39. Furthermore theframe or housing 5 comprises an empty space 41 in a bottom part 43 ofthe frame or housing 5 for receiving said movable pump holding device35. An alternative to a trolley on wheels 39 for the movable pumpholding device 35 can be to provide rails to the frame or housing 5 suchthat the movable pump holding device 35 can be mounted to the rails andmoved along the rails to a position within and at least partly outsidethe frame or housing. However an advantage with providing the movablepump holding device separately on a trolley on wheels 39 is thatvibrations from the pumps when they are running are not transferred tothe rest of the system. This may be a problem in traditional systemswhere the pumps are mounted in the system. Another advantage withproviding the pump main bodies 37 on a movable pump holding device 35according to the invention is that both a less bulky system with pumpscompletely hidden within the system can be achieved while at the sametime good access to the pumps easily can be achieved by moving themovable pump holding device 35 outside the frame or housing 5. Access tothe pumps is for example needed when the disposable tubing set should beexchanged and when maintenance of the pumps is needed. In a traditionalsystem where the pumps are fixedly mounted to the system they need to bemounted such that they both are accessible for connection and formaintenance. This probably requires access from more than one side ofthe pumps. Hereby the systems are often bulky and parts of the pumps areprotruding out from the system. This requires more space in the room.

In the embodiment of the invention as shown in FIGS. 1-3 the frame orhousing 5 comprises four walls 45 a,b,c,d constituting together with aroof 47 of the frame or housing 5 essentially a box 48. Hereby a compactdesign of the base station is achieved. The valves 7 a-f, 9 a-d, 11 a-f,13 a-e, 15 a-f of the frame or housing 5 are in this embodiment of theinvention provided on two of these walls 45 a, 45 c and within anopening 51 of another one of the walls 45 b which will be furtherdescribed below. A first wall 45 a of said four walls comprises anopening 49 for receiving the movable pump holding device 35 into theempty space 41 of the bottom part 43 of the frame or housing 5. In theembodiment shown in FIGS. 1-3 , but not necessarily, a second wall 45 bof said four walls comprises an inlet valve access opening 51 throughwhich access to the inlet valves 7 a-f, 9 a-d of the frame or housing isachieved. Alternatively the inlet valves 7 a-f, 9 a-d are providedmounted to one of the walls 45 a,b,c,d. However an advantage ofproviding the inlet valves 7 a-f, 9 a-d within an opening 51 of one ofthe walls 45 b as shown in FIGS. 1-3 is that the base station will beless bulky and access to the inlets is convenient when the disposabletubing set 21 is provided to the base station 1. Furthermore tubing canbe made shorter and be kept inside the system in an efficient way. Aminimum of tubing length in the disposable tubing set 21 is advantageousfor process efficiency, saving of sample and overall performance andmeasuring accuracy. Hereby the opening 51 is suitably provided in abottom part 43 of the frame or housing 5 close to the movable pumpholding device 35 when the movable pump holding device 35 is providedinside the frame or housing 5. In the embodiment as shown in FIGS. 1-3the second inlet valves 7 a-f are provided on a lower surface 101 of theframe or housing 5 surrounding the opening 51 and the first inlet valves9 a-d are provided on an upper surface 103 of the frame or housingsurrounding the opening 51.

The lower surface 101 is shown to be inclined and the upper surface isshown to be flat however both the surfaces can be either flat orinclined. These are only design alternatives for providing good access.

In the embodiment as shown in FIGS. 1-3 the first wall 45 a alsocomprises the component bypass valves 15 a-f and a third wall 45 ccomprises both the outlet valves 25 a-f and the separation device valves13 a-e. The third wall 45 c is opposite the second wall 45 b in the box48. Furthermore the outlet valves 25 a-f are provided above theseparation device valves 13 a-e on the third wall 45 c referring todirections in the drawings and how the base station will be providedonto a floor. The outlet valves 25 a-f are positioned above theconnection points 71, 73 to the separation device 31 to ensure that allinstruments are fully filled with liquid during operation even at lowflow rates.

Three of the component bypass valves 15 a-c may be for connection of anair trap 63 of the disposable tubing set 21 and the other three of thecomponent bypass valves 15 d-f may be for connection of a filtercartridge 64. An air trap holder 61 and a filter cartridge holder 66 canbe provided on the first wall 45 a. The air trap holder 61 can beprovided on the first wall 45 a of the frame or housing 5 at a higherposition than the pumps. Hereby a raising flow from inlet to the airtrap 63 is provided which is suitable for allowing air to get out fromthe system through the air trap.

The disposable tubing set 21 of the bioprocess system 3 comprises asmentioned above at least one inlet tubing 23 a-j, at least one outlettubing 25 a-f, at least one disposable pump connection part 27, forexample a pump head, which is connected to the inlet tubing 23 a-j andconfigured for being connected to a pump main body 37. The disposabletubing set 21 comprises further according to one embodiment of theinvention at least one disposable air trap 63 and two separation deviceconnection points 71, 73 for connection to a bioprocess separationdevice 31. Said at least one outlet tubing 25 a-f is connected to saidat least one inlet tubing 23 a-j via the other components 27, 63, 71, 73of the disposable tubing set 21.

The disposable air trap 63 is in one embodiment of the invention a swirltype air trap. Such an air trap requires less volume than a traditionalair trap where inlet and outlet both are provided in a bottom of the airtrap. In the swirl type air trap a housing in a cylindrical form isprovided with an inner central rod around which the fluid is circling.An inlet to the cylindrical housing is provided through a wall of thehousing and in a direction such that the fluid provided into the housingis provided along a wall of the housing. Hereby the fluid will swirlaround the inner central rod. An outlet from the air trap is provided ina bottom of the cylindrical housing, i.e. below the inlet. Furthermore aventing opening for letting gas out is provided in the top of the airtrap. The whole air trap 63 is made from plastic and is thus disposabletogether with the rest of the disposable tubing set 21.

The disposable tubing set 21 may further comprise one or more of thefollowing disposable components: a disposable UV sensor, a disposableflow sensor, a disposable air sensor, a disposable pH meter, adisposable conductivity meter and a disposable pressure meter. Accordingto the invention the complete tubing set with components as specifiedabove, such as pump heads, air trap, UV sensors etc. is provided inmaterials suitable for being disposable, i.e. low cost and suitable forbeing gamma irradiated or sanitized in another way. Furthermore thewhole disposable tubing set 21 with its connected components can beremoved in one piece, i.e. all parts connected. Hereby an easy handlingof the product is achieved.

1. A base station for a bioprocess system comprising a frame or housing,wherein said frame or housing comprises a number of valves forcontrolling fluid flow in a disposable tubing set during run of thebioprocess system, such that at least one inlet of the disposable tubingset is connectable to at least one outlet of the disposable tubing setvia a bioprocess separation device of the bioprocess system; and whereina wall of said housing comprises an inlet valve access opening throughwhich access to at least one inlet valve positioned within the frame orhousing is achieved.
 2. The base station of claim 1, wherein the openingis provided in a bottom part of the frame or housing close to a movablepump holding device when the movable pump holding device is providedinside the frame or housing.
 3. The base station of claim 2, wherein thediscrete movable pump holding device comprises at least one pump mainbody, said pump main body comprising a fluid connection configured to bereleasably connectable to a pump connection part of the disposabletubing set.
 4. The base station according to claim 2, wherein saidmovable pump holding device comprises a trolley on wheels and whereinsaid frame or housing comprises a void in a bottom part of the frame orhousing for receiving said movable pump holding device.
 5. The basestation according to claim 1, wherein said frame or housing comprisesfour walls constituting together with a roof of the frame or housingessentially a box, wherein the valves of the frame or housing areprovided on at least three of said four walls and wherein a first wallof said four walls comprises an opening for receiving the movable pumpholding device into an empty space of a bottom part of the frame orhousing.
 6. The base station according to claim 5, wherein outlet valvesof the frame or housing are provided on a third wall of said four walls.7. The base station according to claim 1, wherein at least fiveseparation device valves are provided for receiving the disposabletubing set for controlling feeding of a fluid in the disposable tubingset in either upflow or downflow separation directions or bypass of thebioprocess separation device when connected to the disposable tubingset.
 8. The base station according to claim 5, wherein said at leastfive separation device valves are provided in the third wall of saidfour walls but at a lower position than the outlet valves.
 9. The basestation according to claim 1, wherein said frame or housing comprises aholder for a disposable air trap of the disposable tubing set, whereinsaid holder for a disposable air trap is provided above said inletvalves.
 10. The base station according to claim 1, wherein at least oneof said valves are pinch valves.
 11. The base station according to claim1, wherein a first group of inlet valves are provided on an uppersurface of a frame or housing surrounding the access opening and asecond group of inlet valves are provided on a lower surface of theframe or housing surrounding the access opening.
 12. A bioprocess systemcomprising a base station according to claim 1, and a disposable tubingset.
 13. The bioprocess system of claim 12, further comprising a movablepump holding device operably connected thereto.
 14. A disposable tubingset for use with the base station of claim
 1. 15. The disposable tubingset of claim 14, comprising components including: at least one inlettube; at least one outlet tube; at least one pump connection partconnected to the inlet tubing and configured for being connected to apump main body; at least one air trap; and two separation deviceconnection points for connection to a bioprocess separation device,wherein said components are fluidically interconnected between the atleast one outlet tube and the at least one inlet tube.
 16. Thedisposable tubing set of claim 15, wherein said air trap is a disposableair trap, for example a swirl type air trap.
 17. The disposable tubingset of claim 14, wherein all of the components of the disposable tubingset are fluidically interconnected and the disposable tubing set can beremoved from the base station in one piece.
 18. The disposable tubingset of claim 14, wherein the disposable tubing set comprises twoseparation device connection points, and wherein the disposable tubingis branched such that one branch of the tubing comprises one of theseparation device connection points and another branch comprises theother separation device connection point.
 19. The disposable tubing setof claim 18, further comprising a bypass branch provided in between theother two branches, and optionally wherein the three branches arecollected into one tubing before and after the separation deviceconnection points.
 20. The disposable tubing set of claim 14, furthercomprising one or more of: a filter cartridge; at least one inlettubing; at least one outlet tubing; at least one disposable pumpconnection part, for example a pump head which is connected to inlettubing and configured for being connected to a pump main body; adisposable UV sensor; a disposable flow sensor; a disposable air sensor;a disposable pH meter; a disposable conductivity meter; and/or adisposable pressure meter.